This was a retrospective study exploring the relationship between EVLW and CO and revealing the potential reasons behind CO for lung edema. The results of this study confirmed that the lower the CO, the smaller the tendency of EVLW formation. In addition, this study found that the moderate lower CO in the cardiogenic shock group did not affect the tissue perfusion and renal function. The cardiogenic shock group had the highest 28-day survival rate, which might indicate that less EVLW improved patients’ survival rates.
Increased pulmonary microvascular hydrostatic pressure and increased permeability of the alveolo-capillary barrier could both result in interstitial EVLW. The most pathophysiological hallmark of pulmonary edema is an increase in EVLW, especially in ARDS or other infectious diseases. In this study, the results showed that EVLWI in ARDS was obviously higher than that in other groups in the previous studies. There is no doubt that pulmonary edema resulting from ARDS can be due to the high PVPI, which is also obviously higher than that in the other three groups. Regardless of the ARDS group, our results also suggested that among the remaining three groups, the EVLWI was apparently low in the lower CO groups such as the cardiogenic shock group and the combined shock group, whereas the PVPI in these three groups was nearly the same with no significant difference. According to the formation mechanism of lung water and the Starling principle, we could know the factors that can influence water in the lungs in light of the calculation formula: Qf = kf [(pv – pi) − Δ(πv – πi)] (Qf, extravascular and intravascular lung water; kf, vascular wall permeability index; Δ, reflow index; p, hydrostatic pressure; π, osmotic pressure; v, vascular; i, interstitial).[17,18] This meant that the formation of pulmonary edema could be divided into “pressure type” or “permeability type” pulmonary edema. ARDS is a typical disease that can cause permeability-type edema, which was not the focus of this article. Similar to the other groups in this study, we should explore the other factors that made EVLW different as they had the same PVPI. It may be the first time to report in 1998 that overmuch vascular flow could aggravate lung injury and pulmonary edema. Jozwiak et al suggested that EVLW increased with volume expansion at the same permeability. A higher CO, which meant that there was more volume in the pulmonary vascular that could enhance the hydrostatic pressure, resulted in a high EVLW. These views were in line with the results of this study. Another possible reason to explain our findings was the increased transvascular pressure. Regardless of the colloid osmotic pressure or capillary hydrostatic pressure, the key point of “pressure-type” pulmonary edema was the changing of transvascular pressure.[20,21] The interstitial edema is generated from the pulmonary capillary network around the alveoli. The capillary network and its surroundings are like a black box, as we cannot measure the luminal microvascular pressure and interstitial pressure at the bedside. Although there was no direct indicator in this study to confirm the relationship between CO and transvascular pressure, there was the possible reason that explained the clinical phenomenon. It is well established that typical hydrostatic pressure lung edema is the main clinical manifestation in heart failure patients. However, in our study, we excluded these patients who presented with cardiogenic pulmonary edema at the initial PICCO. The results confirmed our hypothesis that a lower CO could cause a lower EVLW.
In this study, the lung could benefit from tissue-aimed lower CO, and there was no extra injury to organs and tissue perfusion. In the shock resuscitation stage, CO is usually increased by means of fluid treatment to improve oxygen delivery. However, many experiments have shown that excessive fluid therapy and a sustained high-capacity state could be harmful,[23,24] which was an independent risk factor in ICU patients. Sakr et al confirmed that a higher cumulative fluid balance at day 3 after ICU admission was independently associated with an increase in the hazard of death. Cunha et al found that after recovery from shock, the fluid balance continued to rise. Patients who received more fluid treatment spent more time in the ICU and hospital. A clinical investigation designed by Sakr et al revealed that nonsurvivors had a higher fluid balance during the first 4 days as well as cumulative fluid balance and a higher mean ICU stay than survivors in ARDS. During the ICU stay, a higher fluid balance was an independent risk contributing to a higher mortality in ARDS. A multicenter European observational study confirmed that a positive fluid balance was associated with a worse outcome in patients with acute kidney injury. All of the above studies have shown that excessive fluids might result in splanchnic congestion and cause damage to the organs. Thus, it is necessary to find the tissue-aimed lower CO and correspondent volume status for decreasing edema and injury. That means as long as the CO level meets the tissue perfusion and organ function levels, we do not need to increase it. In animal research, restrictive fluid resuscitation could improve oxygenation more than nonrestrictive fluid resuscitation in ARDS. In the “fluids and catheters treatment trial,” patients in the conservative strategy group showed a shorter duration of mechanical ventilation and significantly improved lung function without increasing other organ failures. Goal-directed fluid management, whether for septic shock or cardiogenic shock, could reduce vasopressor use and improve the prognosis.[31,32] Therefore, we hypothesized that the perfusion-aimed lowest CO was the most suitable CO for patients, and the results of this study might support this opinion.
This study revealed that the cardiogenic shock group had the lowest rate of deaths based on the 28-day survival. The most obvious difference between this group and the other three groups was that it had the lowest EVLW. This result at least indicated that lower EVLW was beneficial for patient prognosis, and this lower EVLWI was derived from perfusion-aimed lower levels of CO. To support this opinion, several studies have suggested that administration based on EVLW measurements was safe and effective, reduced the duration of weaning from ventilation, decreased the fluid balance, and improved ICU mortality.[33,34] In a retrospective study of ARDS patients, a decreased EVLW during the first week in ICU yielded a decrease in the day-28 mortality. Except for ARDS patients, other patients with sepsis or septic shock but without ARDS had increased EVLW, possibly reflecting indirect lung injury, as lower EVLW could improve the prognosis. Here, we provided evidence that a lower EVLWI was due to perfusion-aimed lower CO.
This study had several limitations. First, because this was a retrospective study, we did not measure the luminal microvascular and alveolar interstitial pressure. The mean pulmonary artery pressure and pulmonary capillary wedge pressure could be obtained by Swan-Ganz catheterization to assess the microvascular pressure. Esophageal pressure monitoring could be used to evaluate the interstitial pressure. Therefore, prospective randomized control studies should be conducted in the future. Second, as a retrospective study, the number of patients included was small, so the results of this study could only provide a train of thought or possibility, and we still need large sample studies to reach high-quality conclusions. Third, urine output and fluid balance parameters were important for this study. Calculating the volume of liquid appears to be complicated and difficult due to a retrospective study involved a significant proportion of patients received CRRT.
In conclusion, through this retrospective study of the relationship between CO and EVLW under the CHT frame, we found that CHT-oriented resuscitation could reduce the production of EVLW and yield a good prognosis, which might be due to avoiding increasing the CO as soon as the patients’ CO meets tissue perfusion and organ function levels. The most essential contribution leading to better prognosis of critically ill patients has been the cancellation or weakening of ineffective and potentially harmful treatments. We find that increased lung water from CO may be one of the possible mechanisms for an increased EVLW, and this study reveals how to prevent or reduce reinjury from our treatments in clinical work. In the future, more investigations of precise and personalized CHT treatment involving hemodynamic therapy should be performed.
This work was supported by a grant from Capital Characteristic Clinic Project of Beijing (No. Z181100001718209).
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